Goode Travis D, Maren Stephen
Institute for Neuroscience and the Department of Psychology, Texas A&M University, College Station, Texas 77843-3474, USA.
Learn Mem. 2017 Aug 16;24(9):480-491. doi: 10.1101/lm.044206.116. Print 2017 Sep.
Surviving threats in the environment requires brain circuits for detecting (or anticipating) danger and for coordinating appropriate defensive responses (e.g., increased cardiac output, stress hormone release, and freezing behavior). The bed nucleus of the stria terminalis (BNST) is a critical interface between the "affective forebrain"-including the amygdala, ventral hippocampus, and medial prefrontal cortex-and the hypothalamic and brainstem areas that have been implicated in neuroendocrine, autonomic, and behavioral responses to actual or anticipated threats. However, the precise contribution of the BNST to defensive behavior is unclear, both in terms of the antecedent stimuli that mobilize BNST activity and the consequent defensive reactions. For example, it is well known that the BNST is essential for contextual fear conditioning, but dispensable for fear conditioning to discrete conditioned stimuli (CSs), at least as indexed by freezing behavior. However, recent evidence suggests that there are circumstances in which contextual freezing may persist independent of the BNST. Furthermore, the BNST is involved in the reinstatement (or relapse) of conditioned freezing to extinguished discrete CSs. As such, there are critical gaps in understanding how the BNST contributes to fundamental processes involved in Pavlovian fear conditioning. Here, we attempt to provide an integrative account of BNST function in fear conditioning. We discuss distinctions between unconditioned stress and conditioned fear and the role of BNST circuits in organizing behaviors associated with these states. We propose that the BNST mediates conditioned defensive responses-not based on the modality or duration of the antecedent threat or the duration of the behavioral response to the threat-but rather as consequence the ability of an antecedent stimulus to predict when an aversive outcome will occur (i.e., its temporal predictability). We argue that the BNST is not uniquely mobilized by sustained threats or uniquely involved in organizing sustained fear responses. In contrast, we argue that the BNST is involved in organizing fear responses to stimuli that poorly predict danger will occur, no matter the duration, modality, or complexity of those stimuli. The concepts discussed in this review are critical to understanding the contribution of the human BNST to fear and anxiety disorders.
在环境中生存需要大脑回路来检测（或预测）危险，并协调适当的防御反应（例如，增加心输出量、释放应激激素和僵住行为）。终纹床核（BNST）是“情感前脑”（包括杏仁核、腹侧海马体和内侧前额叶皮质）与下丘脑和脑干区域之间的关键接口，这些区域与对实际或预期威胁的神经内分泌、自主神经和行为反应有关。然而，BNST对防御行为的确切贡献尚不清楚，无论是在调动BNST活动的先行刺激方面，还是在随之而来的防御反应方面。例如，众所周知，BNST对于情境恐惧条件作用至关重要，但对于对离散条件刺激（CSs）的恐惧条件作用则是可有可无的，至少以僵住行为为指标是这样。然而，最近的证据表明，在某些情况下，情境性僵住可能独立于BNST而持续存在。此外，BNST参与了对已消退的离散CSs的条件性僵住的恢复（或复发）。因此，在理解BNST如何促成巴甫洛夫式恐惧条件作用所涉及的基本过程方面存在关键差距。在这里，我们试图对BNST在恐惧条件作用中的功能提供一个综合解释。我们讨论了无条件应激和条件性恐惧之间的区别，以及BNST回路在组织与这些状态相关的行为中的作用。我们提出，BNST介导条件性防御反应——不是基于先行威胁的模态或持续时间，也不是基于对威胁的行为反应的持续时间，而是作为先行刺激预测厌恶结果何时会发生的能力（即其时间可预测性）的结果。我们认为，BNST并非仅由持续威胁所调动，也并非仅参与组织持续的恐惧反应。相反，我们认为BNST参与组织对预测危险发生可能性低的刺激的恐惧反应，无论这些刺激的持续时间、模态或复杂性如何。本综述中讨论的概念对于理解人类BNST对恐惧和焦虑障碍的贡献至关重要。
